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Short Note

4-Hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo [5.2.2.02,6]undec-8-ene-3,5-dione

Department of Medical Chemistry, 1st Faculty of Medicine, Medical University of Warsaw, 3 Oczki Street, 02-007 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Molbank 2012, 2012(3), M767; https://doi.org/10.3390/M767
Submission received: 13 March 2012 / Accepted: 17 July 2012 / Published: 26 July 2012

Abstract

:
1-Methyl-7-(propan-2-yl)-4-oxatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (1) as starting material and hydroxylamine were used for the preparation of the title compound 4-hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (2). This product was characterized by 1H-NMR, 13C-NMR, MS and elemental analysis.

Graphical Abstract

1. Introduction

The extensively studied class of cyclic imides is known for a wide spectrum of biological activities. Less examined, but also valuable for their activities are N-hydroxy analogues. They were synthesized as potential β-adrenolytic [1], anxiolytic [2], anti-inflammatory and analgesic agents [3]. Some of the reported derivatives possess metal-chelating abilities, and a number of these compounds inhibits the growth of microorganisms [4]. Additionally, cyclic imides were tested in vitro against various bacteria including Gram-positive cocci, Gram-negtive rods and fungi species (e.g., Candida) [5,6]. The large group of 4-azatricyclo[5.2.2.02,6]undec-8-ene was tested for their affinity to 5-HT1A and 5-HT2A receptors [7]. The most popular method to produce cyclic imides and N-hydroxy analogues is the well-known Diels-Alder reaction [8], but this work describes another conventional method for the synthesis of 4-azatricyclo[5.2.2.02,6]undec-8-ene derivatives [9,10,11]. This one is reserved for N-hydroxy derivatives. The aim of our present work was to prepare 4-hydroxy-1-methyl-7-(propan-2-yl)-4-aza­tricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (2), starting from the corresponding anhydride 1-methyl-7-(propan-2-yl)-4-oxatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (1) using an aqueous solution of hydroxylamine (Scheme 1).

2. Experimental

2.1. General

The melting point was determined in an open capillary and is uncorrected. The NMR spectra were recorded on a Bruker AVANCE DMX400 spectrometer, operating at 400 MHz (1H-NMR) and 100 MHz (13C-NMR). The chemical shift values are expressed in ppm relative to TMS as an internal standard. Mass spectra (ESI) measurements were carried out on a Waters ZQ Micro-mass instrument with a quadrupol mass analyzer. The spectra were recorded in positive ion mode at a declustering potential of 40–60 V. The sample was previously separated on a UPLC column (C18) using a Waters UPLC ACQUITYTM system connected with a DPA detector. Flash chromatography was performed on Merck silica gel 60 (200–400 mesh) using a chloroform/methanol (19:1 vol) mixture as eluent. Analytical TLC was carried out on silica gel F254 (Merck) plates (0.25 mm thickness).

2.2. Synthesis of 4-Hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (2)

A mixture of the anhydride 1 (0.234 g, 1 mmol), K2CO3 (0.20 g, 1.4 mmol), NH2OH·HCl (0.20 g, 2.9 mmol) and H2O (5 mL) was refluxed for 5 h. The precipitate was filtered, washed with water, dried and purified by column chromatography (silica gel) to obtain a white solid.
Yield: 90%.
m.p.: 139–140 °C.
1H-NMR (400 MHz, CDCl3) δ (ppm): 5.97 (d, 1H, CH=, J = 8.4 Hz); 5.89 (d, 1H, CH=, J = 8.4 Hz); 4.18 (br s, 1H, OH); 2.93 (d, 1H, CH-C=O, J = 7.6 Hz); 2.58–2.51 (m, 2H, CH-C=O, CH=); 1.50–1.40 (m, 2H, CH2); 1.46 (s, 3H, CH3); 1.36–1.24 (m, 2H, CH2); 1.08 (d, 3H, CH3, J = 6.8 Hz); 0.98 (d, 3H, CH3, J = 6.8 Hz).
13C-NMR (100 MHz, CDCl3) δ (ppm):174.3, 172.5, 136.3, 48.9, 47.7, 45.1, 43.7, 36.9, 34.2, 29.7, 22.6, 18.4, 16.9.
ESI MS: m/z = 272.4 [M+Na] + (100%).
Elemental analysis: Calculated for C14H19NO3 (249.306): C, 67.45%, H, 7.68%, N, 5.62%. Found: C, 67.48%, H, 7.50%, N, 5.72%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

References

  1. Kossakowski, J.; Jarocka, M. Synthesis of new derivatives of 1-hydroxymethyl and 1-methoxymethyl-dibenzo[e.h]bicyclo[2.2.2]-octane-2,3-dicarboximide with an expected β-adrenolytic activity. Acta Polon. Pharm. 2000, 57, S60–S62. [Google Scholar]
  2. Kossakowski, J.; Krawiecka, M. Synthesis of N-substituted cyclic imides with an expected anxiolytic activity. XXIV. Derivatives of N-hydroxy-1-methoxybicyclo[2.2.2]oct-5-ene-2,3-dicarboximide. Acta Polon. Pharm. 2003, 60, 177–182. [Google Scholar]
  3. Abu-Hashem, A.A.; Gouda, M.A. Synthesis, Anti-inflammatory and Analgesic Evaluation of Certain New 3a,4,9,9a-Tetrahydro-4,9-benzenobenz[f]isoindole-1,3-diones. Arch. Pharm. Chem. Life Sci. 2011, 344, 543–551. [Google Scholar] [CrossRef] [PubMed]
  4. Tanaka, K.; Matsuo, K.; Nakanishi, A.; Kataoka, Y.; Takase, K.; Otsuki, S. Syntheses of Cyclic Hydroxamic Acid Derivatives, and Their Chelating Abilities and Biological Activities. Chem. Pharm. Bull. 1988, 36, 2323–2330. [Google Scholar] [CrossRef] [PubMed]
  5. Struga, M.; Kossakowski, J.; Stefanska, J.; Zimniak, A.; Koziol, A.E. Synthesis and antibacterial activity of bis-[2-hydroxy-3-(1,7,8,9,10-pentamethyl-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yloxy)-propyl]-dimethyl-ammonium chloride. Eur. J. Med. Chem. 2008, 43, 1309–1314. [Google Scholar] [CrossRef] [PubMed]
  6. Struga, M.; Krawiecka, M.; Kossakowski, J.; Stefańska, J.; Miroslaw, B.; Kozioł, A.E. Synthesis and Structural Characterisation of Derivatives of Tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione with an Expected Antimicrobial Activity. J. Chin. Chem. Soc. 2008, 55, 1258–1265. [Google Scholar] [CrossRef]
  7. Bojarski, A.J.; Koziol, A.; Kuran, B.; Kossakowski, J.; Jagiello-Wojtowicz, E.; Chodkowska, A. Synthesis and serotonin receptor activity of the arylpiperazine alkyl/propoxy derivatives of new azatricycloundecanes. Eur. J. Med. Chem. 2009, 44, 152–164. [Google Scholar] [CrossRef] [PubMed]
  8. Ogbomo, S.M.; Burnell, D.J. cis-3,5-Cyclohexadiene-1,2-diol derivatives: Facial selectivity in their Diels–Alder reactions with ethylenic, acetylenic and azo dienophiles. Org. Biomol. Chem. 2006, 4, 3838–3848. [Google Scholar] [CrossRef] [PubMed]
  9. Ishikawa, M.; Fujimoto, M.; Sakai, M.; Matsumoto, A. Les Hydrazides et Hydroxamates Intramoleculaires. III. Sur la Synthese des Homologues d’Hydroxy-2 cis-Perhydroisoindolinedione-1,3. Chem. Pharm. Bull. 1968, 16, 622–625. [Google Scholar] [CrossRef]
  10. Stolberg, M.A.; Mosher, W.A.; Wagner-Jauregg, T. Synthesis of a Series of Vicinally Substituted Hydroxamic Acids. J. Am. Chem. Soc. 1957, 79, 2615–2617. [Google Scholar] [CrossRef]
  11. Bauer, L.; Miarka, S.V. Stereospecific Lossen Rearrangements. J. Org. Chem. 1959, 24, 1293–1296. [Google Scholar] [CrossRef]
Scheme 1. Synthesis of 4-hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo[5.2.2.02,6]un­dec-8-ene-3,5-dione.
Scheme 1. Synthesis of 4-hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo[5.2.2.02,6]un­dec-8-ene-3,5-dione.
Molbank 2012 m767 sch001

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MDPI and ACS Style

Szulczyk, D.; Struga, M. 4-Hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo [5.2.2.02,6]undec-8-ene-3,5-dione. Molbank 2012, 2012, M767. https://doi.org/10.3390/M767

AMA Style

Szulczyk D, Struga M. 4-Hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo [5.2.2.02,6]undec-8-ene-3,5-dione. Molbank. 2012; 2012(3):M767. https://doi.org/10.3390/M767

Chicago/Turabian Style

Szulczyk, Daniel, and Marta Struga. 2012. "4-Hydroxy-1-methyl-7-(propan-2-yl)-4-azatricyclo [5.2.2.02,6]undec-8-ene-3,5-dione" Molbank 2012, no. 3: M767. https://doi.org/10.3390/M767

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